1. Studies with positron emission tomography (PET) have reported that regional cerebral metabolic rates for glucose (rCMRglc) decline with healthy aging in humans. In this study, we showed that such declines likely reflect brain atrophy in the elderly, as they do not occur after rCMRglc were corrected for atrophy. With PET, we measured rCMRglc, before and after correcting for atrophy, in young and older healthy young men while in the "resting" state (eyes covered and ears plugged). Statistically significant mean differences were absent after but not before atrophy correction. Thus, healthy human aging, unlike Alzheimer disease, is not accompanied by reduced resting-state brain glucose metabolism. 2. Brain synaptic activity and energy consumption decline in the course of Alzheimer disease. In a critical review, we proposed that in the first stage of disease, changes in synaptic function reduce neuronal energy demand and lead to potentially reversible downregulation of mitochondrial oxidative phosphorylation (OXPHOS). In a second stage, neurofibrillary tangles with abnormally phosphorylated tau protein accumulate within neuronal cytoplasm, until they co-opt the nonphosphorylated tau necessary for axonal transport of mitochondria between the cell nucleus and the synapse. Severe energy depletion leads to cell death.